title: miR-720 inhibits tumor invasion and migration in breast cancer by targeting TWIST1.
abstract: Breast cancer is the leading cause of cancer death among females, with tumor metastasis being primarily responsible for breast cancer-associated mortality. Current literatures have shown that microRNAs (miRNAs) are implicated in tumor metastasis. In this study, we found that the expression of miR-720 was significantly downregulated in primary breast cancer, with greater downregulation in metastatic tumors. Statistical analysis of 105 cases of primary human breast cancer demonstrated that decreased expression of miR-720 was correlated with lymph node metastasis. Furthermore, reexpression of miR-720 in breast cancer cells remarkably inhibited cell invasiveness and migration both in vitro and in vivo. Mechanistically, downregulation of TWIST1, a promoter of metastasis that was identified as a direct functional target of miR-720, was attributed to the inhibition of metastasis. Consistent with the reduced TWIST1 levels in breast cancer, reexpression of miR-720 upregulated epithelial markers (E-cadherin and β-catenin) and downregulated mesenchymal markers (N-cadherin, fibronectin, vimentin and matrix metalloproteinase-2). Expression of miR-720 was inversely associated with TWIST1 in human breast cancer tissues. Knockdown of TWIST1 expression by small interfering RNA exhibited similar effects to reintroduction of miR-720, whereas overexpression of TWIST1 (without the 3'-untranslated region) abrogated miR-720-mediated metastasis inhibition. Collectively, our data indicate that miR-720 is frequently decreased in breast cancer and manifests antimetastatic activity by downregulating TWIST1, presenting a novel mechanism of miRNA-mediated regulation of tumor metastasis.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People's Republic of China.
authors.forename: Lin-Zi
authors.initials: LZ
authors.lastname: Li
authors.forename: Chris Zhiyi
authors.initials: CZ
authors.lastname: Zhang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.forename: Chun
authors.initials: C
authors.lastname: Yi
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Lu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhao-Jie
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Peng
authors.forename: Yuan-Zhong
authors.initials: YZ
authors.lastname: Yang
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C568636:MIRN720 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1